Disruption of endothelial adherens junctions by high glucose is mediated by protein kinase C-β-dependent vascular endothelial cadherin tyrosine phosphorylation.

Background: Hyperglycemia has been recognized as a primary factor in endothelial barrier dysfunction and in the development of micro- and macrovascular diseases associated with diabetes, but the underlying biochemical mechanisms remain elusive. Tyrosine phosphorylation of vascular endothelial cadherin (VE-cad) leads to the disruption of endothelial adherens junctions and increases the transendothelial migration (TEM) of leukocytes.

Methods: VE-cad tyrosine phosphorylation, adherens junction integrity and TEM of monocytes in human umbilical vein endothelial cells (HUVECs) treated with high-concentration glucose were evaluated.

Sitaxsentan for the treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening, progressive condition that eventually leads to right heart failure. Endothelin receptor antagonists (ETRAs) have been shown to be a safe and efficacious treatment for PAH. Sitaxsentan is a highly selective oral ETRA that, in clinical trials, has demonstrated significant improvements in exercise capacity, functional class and pulmonary hemodynamics in PAH.